Tetrahydro-1, 10-phenanthrolines



3,322,773 TETRAHYDRO-l,IO-PHENANTHRULINEfi Brian Colwell Ennis, Ripponlea, Victoria, Australia, as-

siguor to Monsanto Chemicals (Australia) Limited, West Footscray, Victoria, Australia, a company of Australia No Drawing. Filed Sept. 8, 1964, Ser. No. 395,072 Claims priority, application Australia, Sept. 12, 1963, 35,322/63 8 Uaims. (Cl. 260288) This invention provides new 1,10-phenathrolines, processes for their preparation and fields for their application. The new compounds of the invention are identifiable as 1,2,3,4-tetrahydro-1,IO-phenanthrolines, represented by the structural formula,

r r H CH3 X E d :i: H l T H H H X wherein X is selected from hydrogen, methyl and ethyl. The new compounds of the invention are useful inter alia as intermediates for the preparation of the corresponding parent 1,10-phenanthrolines, and as selective herbicides, as described more fully hereinafter.

The specified new l,2,3,4-tetrahydro-l,10 -phenanthrolines can be prepared by several different methods. One method comprises the reaction of a quinoline selected from S-aminoquinolines and salts of 8-aminoquinolines in which said 8-aminoquinolines are represented by the structural formula,

X- U-X l X X wherein X is selected from hydrogen, methyl and ethyl, with a carbonyl component selected from methyl isopropenyl ketone and precursors which generate such ketone under aqueous acidic conditions, said reaction being effected by heating the quinoline component with the carbonyl component at a temperature up to about 100- C. in the presence of an acidic catalyst. The resultant 1,2,3,4-tetrahydro-l,10-phenant-hroline is recovered from the reaction mixture. Recovery of the crude product, which may be purified, is preferably carried out as hereinafter set forth.

Another method of preparing the new 1,2,3,4-tetrahydro-1,10-phenanthrolines of the invention comprises adding to a suspension of an excess of tin in a hot mineral acid, such as hot hydrochloric acid, a 1,10-phenanthroline of the structural formula,

3,322,773 Patented May 30, 1967 action product. Recovery of the crude product, which may be purified, is preferably carried out as described below.

I prefer to prepare the new 1,2,3,4-tetrahydro --1,10- phenanthrolines by the reaction of a quinoline with methyl isopropenyl ketone or a precursor of methyl isopropenyl ketone in the presence of an acid catalyst, as indicated above. Thus, in carrying out the preferred method, the reaction components desirably are heated to a temperature within the range of 30-90 C. I have found that formation of tetrahydrophenanthroline is uneconomically slow below 30 C., and that some degradation of the aminoquinoline may occur above about C., the reaction being complete within about two hours at a temperature of 60 70 C., which is the preferred temperature range. Optimum results are obtained if a slight molar excess of the methyl isopropenyl ketone component or precursor of methyl isopropenyl ketone, based on the aminoquinoline, is used, as there is a tendency for the carbonyl component to be lost through polymerization. The reaction is only slightly exothermic; however, better control of the reaction temperature results if the methyl isopropenyl ketone or precursor component is added gradually to a stirred mixture of the aminoquinoline and acid catalyst. At the end of the reaction, any excess of methyl isopropenyl ketone may be recovered by distillation. The residue is then basified to liberate the desired tetrahydro-1,10-phenanthroline and by-product parent alkyl substituted 1,10-phenanthroline, which is always obtained as a reaction (Jo-product. The desired tetrahydro-1,1'0-phenanthro-line is then separated from the by-product parent 1,10-phenanthroline and may be purified as hereinatfer described.

Utilizing the preferred method of preparation as described above, l,2,3,4-tetrahydro-3,4,7,S- tetramethyI-l, 10-phenantholine can be prepared by reacting 3,4-dimethyl-8-aminoquinoline with methyl isopropenyl ketone or a precursor compound (such as 1-hydroxy-2-methylbuta-n-3-one, which gives the indicated unsaturated ketone under aqueous acidic conditions) in the presence of an acid catalyst. Examples of 8-aminoquinolines, other than 3,4-dimethyl-8-aminoquinoline, which may be used in the process of the invention include 8-aminoquinoline; 3- methyl-8aminoquinoline; 2,4-dimet-hyl 8 aminoquinoline; 3,5,6-trimethyl-8-amin-oquinoline; 3,4-dimethyl-5,'6- diethyl-8-aminoquinoline; 3,4,5, 6-tetramethyl 8 aminoquinoline; and 4-methyl-8-aminoquinoline. Acid addition salts of the 8-aminoquinolines which can be used in the process of the invention include the salts of the mineral acids, e.g., the hydrochloride or sulfate salts. In some cases, an acid addition salt such as the hydrochloride may be preferred in providing acidic conditions for use in conjunction with precursors for generating the methyl isopropenyl ketone component.

As employed herein, the phase precursors of methyl isopropenyl ketone connotes those materials which are readily converted to said ketone upon treatment with mineral acid and water. The nature of such precursors, and their use in Sk-raup-type reactions, is known to the art.

Methyl isopropenyl ketone and other such [i-vinyl ketones are often prepared by condensing an aldehyde with a methylene group which is alpha to the carbonyl group of the ketone, followed by dehydration of the resultant ,o-hydroxy ketone to the required B-vinyl ketone. Thus, methyl isopropenyl ketone is commonly prepared by condensing formaldehyde with methyl ethyl ketone, which gives l-hydroxy-2-methylbutan-3-one as intermediate, and this intermediate may be dehydrated by heating in the presence of a mineral acid catalyst to give methyl isopropenyl ketone. Accordingly, it is sometimes more convenient to use such a precursor of methyl isopropenyl ketone as a reactant in the synthesis of the tetrahydro- 1,10-phenanthrolines of this invention, the desired ketone being generated in situ (i.e., by the use of l-hydroxy-Z- methylbutan-3-0ne as the carbonyl component). Precursors of methyl isopropenyl ketone useful for carrying out the process of the invention can be represented by the structural formulae,

i HzC-CH- CH Y CH3 wherein Y is selected from hydroxy, alkoxy, acetoxy and halogen; and wherein Z is selected from alkoxy, acetoxy and halogen. In these cases, the alkyl and alkoxy groups preferably contain from 1 to 4 carbon atoms, and the halogen is preferably chlorine. Examples of such pre- 7 chloric, hydrobromic, hypophosphorous and sulfuric acids. Acids such as nitric or arsenic acids, which can function as oxidizing agents, should not be used. The amount of acid taken may be varied within wide limits.

' With the weaker acids, it is generally necessary to have suflicient acid to at least neutralize the basicity of the aminoquinoline, the amount of acid used usually being governed by the solubility of the amine salt. A minimum of one mol of acid catalyst, based on the aminoquinoline component, should be employed, preferably in excess of one mol of acidbeing used. Acetic acid is particularly convenient for use as the acid catalyst, since an excess of acetic acid serves as a good solvent for both the reaction components and products. However, other solvents or diluents such as water, or inert organic liquids such as benzene, may be used for the reaction components and products.

The desired tetrahydro-l,lO phenanthroline present in the reaction product of the preferred method can be readily separated from the by-product parent 1,10-phenanthroline and then purified by conventional means. The tetrahydro-1,10-phenanthrolines are freely soluble in nonpol-ar solvents, whereas the by-pro'duct parent 1,10-phenanthrolines are virtually insoluble in such solvents. A preliminary separation from by-product 1,10-phenanthroline is therefore easily achieved by extraction of the neutralized reaction product indicated with a solvent such as petroleum ether, cyclohexane or benzene. The tetrahydro- 1,10-phenanthroline in the extract may then be' further purified by chromatography, crystallization or fractional distillation under reduced pressure or by a combination of these methods. As the tetrahydro-1,lO-phenanthroline is a low-melting solid, it is also convenient to prepare the picrate or trinitro fiuorenone complex, both of which are high-melting solids which can be readily purified by crystallization, the desired tetrahydro-1,10-phenanthroline then being regenerated from the purified derivatives.

7 The following non-limitative practical examples illustrate the preparation of the new compounds of the invention.

Example 1 A solution of 3,4-dimethyl-8-aminoquinoline (5 g.) in hydroxymethyl butanone 4 ml.) and glacial acetic acid (5 ml.) was stirred on a steam bath for one hour. It was then diluted with water ml.) and extracted with benzene. The aqueous layer was neutralized with sodium hydroxide solution, and the resultant solid was washed with cold benzene (20 ml.). The combined benzene extracts were washed with water, dried (MgSO and chromatographed on a column of alumina. The impure tetrahydro 1,10-phenanthroline was obtained as a thick yellow oil which slowly crystallized (3.0 g.; 45% This was purified by way of the picrate, M.P. 195.5- 196 C., from which the base was recovered by treatment with 10% sodium hydroxide solution. Crystallization from methanol then gave the 1,2,3,4-tetrahydro-3,4, 7,8-tetramethyl-1,10-phenanthroline as yellow needles, M.P. 7272.4 C. Analysis.-Found: C, 80.0; H, 8.3, N, 11.7 for C H N and requires C, 79.9; H, 8.4; N, 11.7%.

Example 2 3,4-dimethyl-8-aminoquinoline (3.4 g.) and hydroxymethylbutanone (2.5 g.) were heated under reflux in aqueous hypophosphorous acid (20 ml.) for one hour. The reaction mixture was diluted with water and neutralized with sodium hydroxide solution. The solid was recovered, dried and extracted with petroleum ether (B.P. 4060 C.). The tetrahydro-1,10-phenanthroline in this extract was purified as in Example 1, giving a yield of 40%.

Example 3 Repetition of Example 2 with sulfuric acid (40% w./w.) in place of the hypophosphorus acid gave a yield of tetrahydro-1,IO-phenanthroline of 34% of the theoretical.

Dehydrogenation or oxidation of the new 1,2,3,4-tetrahydro-1,l0-phenanthrolines of the invention, so as to form the parent 1,10-phenanthrolines, can be effected by a number of methods; for example, by (a) using arsenic acid plus hydrochloric or hydrobromic acid mixtures, or (b) using sulfur, or (c) using air/platinum dioxide oxidation. The preferred method is the use of arsenic acid/ hydrochloric acid mixtures, the tetrahydro-1,10-phenanthroline being oxidized smoothly to the parent 1,10- phenanthroline by heating with such acid mixtures. According to the preferred method, a l,2,3,4-tetrahydro- 1,10-phenanthroline as specified is heated at a temperature within the range of 130 C. in the presence of arsenic acid in association with a hydrohalic acid selected from hydrochloric acid and hydrobromic acid, and the resultant alkyl substituted 1,10-phenanthroline of the structural formula,

x x CH3 I x wherein X is selected from hydrogen, methyl and ethyl, is recovered from the reaction mixture.

The dehydrogenation or oxidation reaction is slow, between about 5-10 hours and generally about 7 hours being required for completion at the reflux temperature at atmospheric pressure. Reaction time can be reduced by operating at higher pressures and temperatures. Using a hydrochloric acid/ arsenic mixture as the dehydrogenation or oxidation reagent, a reaction time of 6-8 hours is required at the reflux temperature of the mixture for complete conversion of said tetrahydro compound to the desired 1,10-pl1enanthroline. Hydrochloric acid is preferred to hydrobromic acid since it is cheaper and freely avialable. It also gives a satisfactorily fast reaction rate and high yield of the desired product. A minimum of 3 mols of such acid, based on the tetrahydro compound, should be used, the maximum amount not being particularly critical. As much as 20 mols is usable, and about to mols is usually required in order to maintain a suitably fluid reaction mixture for ease of work- 6 Example 6 1,2,3,4-tetrahyd-ro 3,4,7,8-tetramethyl 1,10-phenanthroline (0.2 g.) and platinum dioxide mg.) were ing. The concentration of such acid is not critical, but it 5 heated under reflux in acetic acid for 6 hours is preferably adjusted so that the final mixture approxi- While a 510W Stream Of air was Passed through the mates the constant boiling mixture at atmospheric pres- The mixture was diluted With Water and sure. The ar eni a id i d i th f of arsenic filtered. The filtrate was basified, and the resultant pentoxide or as the 80% arsenic acid of commerce. The Pfeduct was washed With behZehe to give the Parent minimum amount of arsenic used in the process should 10 lilo-phenanthroline be 2 mols beased on the tetrahydro compound, preferably esides being useful as intermediates for the preparanot more than 3 mols being used due to th o t of tion of the parent 1,10-phenanthrolines, the new l,2,3,4- arsenic acid. tetrahydro-l,1*0-phenanthrolines of the invention are use- The following non-limitative practical example illusful inter alia in the destruction of undesired vegetation trates the preparation of the parent 3,4,7,8-tetraalkyl-1, 15 and in the selective control or inhibition of plant growth. IO-phenanthroline from the corresponding tetrahydro- Thus, said tetrahydro-l,l0-phenanthrolines act as postphenanthroline using hydrochloric acid/ arsenic acid as emergent herbicides toward a variety of plants, but have the dehydrogenation or oxidation medium. no effect upon wild oats, a plant related to wheat, which enables said compounds to find application as a selective Example 4 2 herbicide. Desirable herbicidal eifects can be obtained 1,2,3,4-tetrahydro 3,4,7,8 tetramethyl 1,10-phenby the application of small amounts, e.g., one-half pound anthroline (0.4 g.) was heated under reflux for 7 /2 hours P acre, of y of the compound- However, with concentrated hydrochloric acid (15 ml.) and 80% amellhts as high as y P011lnds P acre may be necesarsenic acid (1 ml.). The reaction mixture was poured sary or desirable in some instances. For general applicainto water (15 ml.) and neutralized with sodium hytion as a pee-emergence herbicide. amounts in the range droxide solution. The resulting solid was dried and ex- 0f Pounds p acre of the Compound ean he used, tracted with benzene, leaving the parent 1,10-phenanthrogreater selectivity being obtained at the lower concenline (0.38 g., 97%), M.P. 272277 C. tration. Herbicidal activity of the new tetrahydro-LIO- Another method for the dehydrogenation of the tetraphenanthroline compounds was ascertained in experihydrol,10-phenanthroline to the parent 1,10-phenanthromehts eohdlleted 0h Dre-emergence and posteemefgehee or line as indicated involves reaction of the tetrahydro-l, con -act h r ici l s re ning es on plants sing the IO-phenanthroline compound with sulfur. The tetrahydrofollowing species of plants: 1,10-phenanthroline is stirred and heated with sulfur at a temperature of 130-160" 0, preferably at 140 1so Graes' Fextall C. Hydrogen sulfied is evolved, and the melt slowly B Bmadleaf cliahgrass solidifies as the parent LID-phenanthroline is formed. MQTmhg glory PlgWeed An excess of sulfur may be used to serve as a diluent Wlld Oat Soybean if required. At the end of the reaction, the parent 1,10- Bromegfess Wild huekWhee"t phenanthroline may be extracted from the excess of sul- F. Ry Tomato fur with dilute acid and purified by usual procedures. 40 G. Radish SOTghum The following non-limitative practical example illustrates Sugar beet this particular method.

Example 5 The results of the tests are recorded in Table I below.

In the pre-emergence herbicidal screening tests, alutetfahydro r ethy1- 1,10-phenminium tins with perforated bottoms were filled to a anthroline (1.0 g.) and sulfur (1.0 g.) were stirred todepth 0f 2 /s". Seeds of -each species" were laid on the at 140-4450' for 6 hours- Product Was surface of the soil and covered with soil to the top edge cooled, crushed and extracted dlluifi sulfuric acid. of the pans were then on a flooded Neutralizatlon of the ac d-extract gave a solid, which greenhouse bench E h g" X 3" pan was Sprayed with a h collectfid w g ig g g iif a solution of the candidate herbicide at the rate speci- Wl a Sma amoun o ,nzene glve e Pawn e fied in Table I. The spray was then applied uniformly rzniestl iycl3 1,1-0-phenanthrol1ne, 0.69 g. (70%), to the surface of the soil. The procedure for evaluating Yet another method for the dehydrogenation of the i i herbicldal i to g g' tetrahydro-1,10-phenanthroline to the parent 1,10-phen- Sam 6 upre-gmergence. rea a except t at 6 S anthroline as indicated involves oxidation with air/platwere a to gemmfate an grow a pfinod of 14 inum dioxide. The tetrahydro-l,lo-phenanthroline, at a to days before slzfraymg Pan Wlth 6 of a temperature of about C is contacted with air in the solution of the candidate herbiclde. The herbicidal ratings, presence of platinum dioxide as a catalyst. Dehydroboth pqstemergence or Contact and Preemergeme, genation proceeds at a satisfactory rate, and the parent corded 111 Table I are! 1,10-phenanthroline is formed in about 60% yield. Al- Plant d ad ternatively, the reaction can conveniently be carried out (3) Severe phytotoxicity at lower temperatures, using acetic acid as .a reaction me- (2) Moderate phytotoxicity dium. The following non-limitative practical example (1) Slight phytotoxicity illustrates this particular method. (0) No phytotoxicity TABLE I Herbicidal Activity Treatment l l l l l l l l l l V I I 25 lb./aere 1,2,3,4-tetrahydro-3,4,7,8-tetramethyl-l,IO-phenanthroline 0 1 2 0 0 0 2 3 0 3 0 0 0 0 0 0.5% contact 1,2,3,4-tetrahydrc-3,4,7,8-

tetramethyl-l,IO-phenanthroline 2 2 0 0 4 2 4 3 4 4 4 3 1 4 2 In employing the tetrahydrophenanthrolines of this invention, it will be recognized that these compounds can be applied to the plant parts. As is apparent from the demonstrated preand post-emergent activity, the phrase plant parts includes not only stems, branches and foliage, but also In the field application of the compounds of the invention, they are most conveniently applied as herbicidal compositions containing from about 0.5% to about 95% by weight of the active compound. These herbicidal compositions or formulations can be prepared by admixing the active compound, or a mixture of such compounds, with an inert carrier or diluent material, the resultant compositions being ready for application to soil containing undesired post-emergent or pre-emergent vegatation, using conventional equipment for the purpose. Thus, the herbicidal compositions or formulations can be prepared in the form of solids or liquids.

Solid compositions are preferably in the form of dusts and are compounded to give homogeneous, free-flowing dusts by admixing the compound with finely-divided inert carriers such as t-alcs, clays, lime, bentonite, pumice, fullers earth, pyrophyllite, diatomaceous earth, or flours such as walnut shell, wheat, redwood, soya bean, cottonseed fl-ours and other inert solid materials of the kind conventionally employed in preparing herbicidal compositions in dusts or powdered form. On the other hand, such inert carriers can be impregnated with the present compounds by means of a volatile solvent. These carriers or diluen-ts can represent a substantial portion (for example, 50- 95% by weight) of the entire formulation as applied.

Liquid herbicidal compositions can be prepared by admixing the new compounds of the invention with a suitable liquid inert carrier or diluent. The new tetrahydrophenanthorilnes of the invention are not water-soluble. However, they are soluble in organic solvents such as kerosene, xylene, toluene and high-aromatic naphthas. The proportion of such organic solvent to be used in the formulations will depend upon the solubility of the active compound and may require as little as 1% or as much as 90% or more in order to provide a uniformly distributed formulation.

The herbicidal compositions of the invention, whether in the form of dusts or liquids, preferably include also an organic surfactant of the kind sometimes referred to in the art as a wetting, dispersing or emulsifying agent. These surfactants have several functions, such as causing the compositions to be easily dispersed in water to give aqueous sprays which, for the most part, constitute desirable media for most applications. They also help in wetting the surfaces of the undesired plants to which a formulation is applied. The organic surfactants employed can be of the anionic, cationic or nonionic type. Generally, the surfactants will be only a minor proportion of the formulation as used, for example, less than 15% and frequently as low as 0.05% by weight of the composition. Usually concentrations of from 0.5% to 5% are found to be optimum.

Thus, the new compounds can be incorporated into absorbent materials such as clays, fullers earth and the like, together with wetting agents such as alkyl naphthalene sulfonate and dispersing agents such as lignin sulfonates, to produce a water-dispersible powder which can be suspended in water as a carrier and sprayedonto the soil so as to provide a treatment of 05-25 pounds per acre. Emulsifiable herbicidal concentrates of the new compounds can likewise be formulated, for example, using kerosene, xylene, toluene or a high aromatic naphtha as solvent, the emulsifier used being nonionic, such as the octyl or nonyl phenol-ethylene oxide derivatives, e.g., Triton X100, or preferably blends of nonionics with oilsoluble anionic surfactants such as the calcium salt of an alkyl aryl sulfonate. A blend known as Emcol M500X givesparticularly good results. The emulsifiable concenroots and germinant seeds as well.

trate may contain between 20% and 30% of the active compound on a weight/volume basis.

Examples of emulsifiable formulations in accordance with the invention are as follows:

Xylene to mls.

1 Triton is the trademark of Rohni & Haas C0., U.S.A.

2 High aromatic naphtha, e.g., Sovacide FY (11 Vacuum Oil product) or solvent 250/300 (an Esso product).

3 Emcol is the trademark of Emulsol Corporation, U.S.A. These concentrates can be readily mixed with water as a carrier and sprayed onto weeds or the soil so as to provide a treatment of 0.5 to 25 pounds per acre.

While the invention has been described herein with regard to certain specific embodiments, it is not so limited. It is to be understood that variations and modifications thereof may be made by those skilled in the art without departing from the spirit and scope of the invention.

What is claimed is:

1. A compound of the formula,

H CH3 X HaC\ X H N i H H H tetramethyll lO-ph enanthroline.

6. l,2,3,4-tetrahydro 3,5,6,7,8-pentamethyl 1,10- phenanthroline.

7. 1,2,3,4 tetrahydro 3,4,7,S-tetramethyl-5,6-diethyl-1,l0-phenanthroline.

8. 1,2,3,4 tetrahydro 3,4,5,6,7,8-hexamethyl-1,10 phenanthroline.

References Cited OTHER REFERENCES Badger et al.: Aust. J. Chem, vol. 16, 814 to 827, 840 to 844 (1963)..

Case: I. Am. Chem. Soc., vol. 70, pp. 3994 to 3996 (1948).

Elderfield: Heterocyclic Chemistry, pp. 21 to 24 and 394 to 400.

Grigg et al.: Aust. J. Chem, vol. 15, 864 to 866 (1962).

vol. IV, Wiley, 1952,

ALEX MAZEL, Primary Examiner. D. G. DAUS, Assistant Examiner. 

1. A COMPOUND OF THE FORMULA, 